Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormonal receptors and markers for prognostic evaluation were detected immunohistochemically in 196 infiltrating ductal breast carcinomas. Immunohistochemical detection of progesterone and oestrogen receptor is a method giving results generally concordant with those of the binding assay. However, immunohistochemical detection seems better. It allows the detection of hormonal receptors on small carcinomas, it is not modified by the endogenous hormones, and it has a slightly better correlation with prognosis and with the response to hormone therapy. Immunohistochemical detection of progesterone receptor has a prognostic value, sorting a negative subgroup with a poor prognosis from the oestrogen receptor positive tumours. These results can be obtained without quantitative immunohistological methods. ERD5, pS2, HSP27 and cathepsin D are associated with oestrogen receptor positivity. pS2 and HSP27 are interesting markers. They characterize a subgroup of oestrogen receptor negative tumours with a good prognosis. Moreover, pS2 is a marker of response to hormone therapy. ERD5 and cathepsin D do not appear to be of value as markers of prognosis.
Histopathology 1993 Sep
PMID:Oestrogen receptor, progesterone receptor, pS2, ERD5, HSP27 and cathepsin D in invasive ductal breast carcinomas. 822 42

Expression of pS2 was studied by immunocytochemistry in normal breast tissue (n = 20), benign tumours (n = 9) and 145 breast cancers representative of the different histological types. pS2 immunostaining was scored as negative (D1 = 0-5% stained cells), positive (D2 = 5-75% stained cells) or highly positive (D3 > 75% stained cells). pS2 protein was evident in all normal breast samples examined. Six of nine benign lesions showed pS2 staining. In both cases, immunostaining was weaker than in breast cancers. Of breast cancers, 77/145 (53.1%) were pS2 positive, including 33.1% with intense staining. The presence of pS2 was not correlated with the age of patients, the size of the primary tumour, or lymph node status, but was correlated with histological grading and nuclear grading. pS2 expression was also correlated with menopausal status and oestrogen receptor status (59% of receptor-positive tumours were pS2 positive), but not to progesterone receptor status. pS2 expression in breast carcinomas is not a characteristic of specific histological types. Although this protein is predominantly expressed in oestrogen receptor-positive and differentiated tumours, it shows oestrogen-independent expression in about 30% of cases.
Histopathology 1993 Sep
PMID:Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours. 822 43

A new complementary DNA, p27, has been cloned and sequenced from estradiol-treated MCF7 human breast carcinoma cells. It encodes a putative highly hydrophobic protein of 122 amino acids which has a 33% overall sequence similarity to the product of the 6-16 gene (R. L. Friedman, S. P. Manly, M. McMahon, I. M. Kerr, and G. R. Stark, Cell, 38: 745-755, 1984), which is transcriptionally induced by interferons of the alpha/beta type. We demonstrate here that the p27 gene, which is located in band q32 of human chromosome 14, is also induced by interferon-alpha in human cell lines of different origin and that expression is independent of the presence of estradiol receptor in the cells. High levels of p27 RNA were found in vivo in approximately 50% of primary human breast carcinomas (21 were tested by Northern blotting). In situ hybridization to some of the p27-overexpressing tumors showed that the p27 RNA is localized in cancer cells and sometimes also in fibroblastic cells of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estrogen-induced pS2 gene. Further studies are now necessary to elucidate the cause of p27 gene overexpression in breast carcinoma and in particular to determine whether it corresponds to chromosomal rearrangements in the 14q32 region and/or to induction by interferons of the alpha/beta type.
Cancer Res 1993 Sep 01
PMID:Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma. 835 38

By using a combination of the methods of reverse transcription-PCR and rapid amplification of cDNA ends, a cDNA for rat pS2 peptide (rpS2) was successfully cloned and sequenced from rat stomach. By RNA blot analysis, the gene was shown to be expressed abundantly in the stomach and only faintly in the duodenum, but not in other tissues including the distal small and large intestines. rpS2 expression was also examined in the rectum during the course of acetic acid-induced colitis; rpS2 mRNA was detected during the acute phase of colitis but not in normal controls or during the recovery phase. On the other hand, expression of rat intestinal trefoil factor (rITF) was down-regulated during the acute phase of colitis and then up-regulated during the recovery phase, whereas rat spasmolytic peptide was not detectable throughout the course of the induced colitis. These results indicate that the patterns and timing of the expression of these trefoil peptides are different from each other. rpS2 may play an important role in the proliferation of intestinal epithelial cells during the acute phase of mucosal ulceration, whereas rITF may be involved in differentiation of the cells, particularly to form goblet cells, during the recovery phase.
Biochem J 1996 Sep 15
PMID:cDNA cloning of rat pS2 peptide and expression of trefoil peptides in acetic acid-induced colitis. 883 41

Regulation of two genes involved in tumor invasion, the matrix metalloproteinase (MMP)-1 and the tissue inhibitor of MMP (TIMP)-1, by activators of protein kinase C (PKC) or protein kinase A (PKA) was studied in MCF-7 mammary adenocarcinoma cells. The basal mRNA expression was undetectable for MMP-1 and low for TIMP-1. Treatment of MCF-7 cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 nM) was associated with a high expression of MMP-1 mRNA, as well as an induction of the level of TIMP-1 mRNA (5- to 10-fold). In the presence of actinomycin D (AMD, 4.0 microM), an inhibitor of transcription, these stimulatory effects of TPA were abolished. Similar responses were observed when protein synthesis was inhibited by cycloheximide (CHX, 50 microM). In the presence of the cyclic AMP (cAMP) analogue N6-benzoyl (N6-Bzl)-cAMP (500 microM), the MMP-1 mRNA was unaffected and still below the level of detection, whereas a non-significant increase (< 2-fold) in TIMP-1 mRNA was observed. The level of pS2 mRNA, of which the induction by TPA in MCF-7 cells is a primary transcriptional event, was up-regulated (10- to 15-fold) by TPA (100 nM), whereas a much weaker increase (2- to 3-fold) was observed by treatment with N6-Bzl-cAMP (500 microM). Again, these stimulatory effects were counteracted by AMD (4.0 microM) and CHX (50 microM). These data suggest that activation of PKC but not of PKA may induce transcription of MMP-1 and TIMP-1, possibly by the synthesis of transcription factor(s), in transformed cells of epithelial origin.
Clin Exp Metastasis 1996 Sep
PMID:Regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in MCF-7 cells: comparison with regulatory mechanisms of pS2 expression. 887 12

Plasmids expressing different domains of the hepatis C virus (HCV) envelope E2 glycoprotein from a genotype 1a isolate were constructed to compare the immunogenic potential of E2 in nucleic acid-based immunizations. One plasmid, pCIE2t, expressed a C-terminally truncated form of E2, while others, pS2.SE2A to pS2.SE2E, encoded the adjacent 60-amino-acid (aa) sequences of E2 (inserts A to E) expressed as a fusion with the hepatitis B virus surface antigen. BALB/c mice were given injections of the plasmids intramuscularly (i.m.) or intraepidermally (i.e.) via a gene gun (biolistic introduction), and induced humoral immune responses were evaluated. The i.e. injections resulted in higher seroconversion rates and antibody titers, up to 100-fold, than did the i.m. injections (P = 0.01 to 0.04). Three restricted immunogenic domains, E2A (aa 384 to 443), E2C (aa 504 to 555), and E2E (aa 609 to 674), that yielded antibody titers ranging from 1:59 to > 1:43,700 could be identified. Subtype 1a- and 1b-derived E2 antigens and synthetic peptides were used in Western blot and enzyme-linked immunosorbent assay analyses, which revealed that the cross-reactivity of the plasmid-induced antibodies was linked both to the type of antigen expressed and to the injection mode. Induced anti-E2 antibodies could immunoprecipitate noncovalent E1E2 complexes believed to exist on the surface of HCV virions. This study allowed us to identify restricted immunogenic domains within E2 and demonstrated that different routes of injection of HCV E2 plasmids can result in quantitatively and qualitatively different humoral immune responses.
J Virol 1997 Sep
PMID:Immunization with plasmid DNA encoding hepatitis C virus envelope E2 antigenic domains induces antibodies whose immune reactivity is linked to the injection mode. 926 44

The three human trefoil proteins pS2, human intestinal trefoil factor (hITF), and human spasmolytic polypeptide (hSP) are expressed principally in the mucosa of the gastrointestinal tract. They are also expressed in a variety of other normal tissues and tumours. This review discusses the pattern of expression of trefoil proteins in cancer, current views on the biological functions of trefoil proteins, and the way in which the expression of trefoil proteins may influence the behaviour of cancer cells.
J Pathol 1997 Sep
PMID:Trefoil proteins: their role in normal and malignant cells. 937 Sep 40

pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The relationship to the expression of other trefoil peptides, human spasmolytic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-TFF 3) is documented here. Fifty-seven breast specimens were selected from surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas in situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive ductal carcinomas (IDC), and seven invasive lobular carcinomas (ILC). The comparative distribution of trefoil mRNAs was assessed by in situ hybridization using 35S-labelled riboprobes and immunohistochemical staining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign breast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, LCIS and ILC, and 21/24 IDC. Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptide or mRNA was not detected in any of these cases. MCF 7 breast carcinoma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not hSP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a prognostic factor, but also raises questions about the regulatory pathway for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cell motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a heterodimer or compete for receptor binding. Absence of hSP-TFF 2 expression may be of equal relevance to tumour cell biology.
J Pathol 1997 Sep
PMID:Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium. 937 Sep 44

To elucidate the mechanisms responsible for the development of anti-estrogen resistance, we have cloned and established 3 stable ICI-182,780-resistant sub-lines, MCF-7/182R-1, MCF-7/182R-6 and MCF-7/182R-7 from the estrogen-receptor(ER)-positive and estrogen-responsive human breast-cancer MCF-7 cell line by long-term treatment with 10(-7) M ICI 182,780. The ICI-182,780-resistant MCF-7 sub-lines express ER, but compared with MCF-7 cells the level is significantly lower in all 3 sub-lines. In the MCF-7 cell line we find that ER expression is regulated by estrogen and anti-estrogens at the transcriptional and post-transcriptional level. This is in contrast to the ICI-182,780-resistant sub-lines, in which we find very little hormonal effects on the ER mRNA expression level. The resistant sub-lines also deviate from parent characteristics by the complete lack of expression of progesterone receptor even when grown in the presence of estradiol. All 3 resistant sub-lines have a lower basal expression of cathepsin-D mRNA comparable with the lower ER expression, but, in contrast, they have higher basal expression of the pS2 mRNA than the parent MCF-7 cell line. Although there are different basal expression levels of the pS2 and cathepsin-D genes, the resistant sub-lines behave like the parent MCF-7 cell line with respect to the hormonal regulation of both genes. The estrogen receptors in the resistant sub-lines have also maintained wild-type characteristics with respect to estrogen and anti-estrogen regulation of the estrogen-regulated proteins procathepsin D, alpha1-antitrypsin and a 42-kDa protein. The resistant cells require estrogen for growth in athymic nude mice. Our results clearly demonstrate that the ER in the resistant sub-lines have a normal function for most parameters investigated, supporting our earlier observation that only wild-type ER protein is expressed in these cells. The few observed differences in ER function between the parent MCF-7 cell line and the resistant sub-lines are not likely to be responsible for the ICI-182,780-resistant phenotype.
Int J Cancer 1997 Sep 17
PMID:Resistance of human breast-cancer cells to the pure steroidal anti-estrogen ICI 182,780 is not associated with a general loss of estrogen-receptor expression or lack of estrogen responsiveness. 937 50

Cathepsin D trafficking is altered in cancer cells, leading to increased secretion of the pro-enzyme, which can be reinternalized by the same cancer cells and by stromal cells. We studied pro-cathepsin D endocytosis in two human breast cancer cell lines (MDA-MB231, MCF-7) and in human normal fibroblasts. Pro-enzyme uptake was studied indirectly through immunofluorescence analysis of anti-pro-cathepsin D monoclonal antibodies internalized in living cells. Both cancer cell lines internalized the pro-cathepsin D-antibody complex into endosomal compartments in the presence of 10 mM mannose-6-phosphate. Non-malignant fibroblasts, which do not secrete pro-cathepsin D, only internalized anti-cathepsin D antibody when purified pro-cathepsin D was added and this endocytosis was totally inhibited by mannose-6-phosphate. Cathepsin D endocytosis in cancer cells was not mediated by lectins or another receptor binding the cathepsin profragment. It was not due to fluid endocytosis, since another protein pS2 secreted by MCF-7 was not endocytosed with its antibody in the same conditions. Double-immunofluorescence and confocal microscopy analyses revealed that antibodies specific to pro-cathepsin D (M2E8) and to the mannose-6-phosphate/IGFII receptor were co-internalized independently in non-permeabilized MDA-MB231 cells and MCF-7 cells, but not in fibroblasts. Moreover, when metabolically labelled pro-cathepsin D secreted by MCF-7 or MDA-MB231 cells was incubated with homologous or heterologous non-radioactive cells, the time-dependent uptake and maturation of the pro-enzyme into fibroblasts were totally inhibited by mannose-6-phosphate, whereas they were not in the two breast cancer cell lines. The percentage of mannose-6-phosphate-independent binding of radioactively labelled pro-cathepsin D to MDA-MB231 cells at 16 degrees C was higher (7-8%) at low pro-cathepsin D concentration than at high concentration (1.5%), indicating the presence of saturable binding site(s) at the cell surface that are different from the mannose-6-phosphate receptors. We conclude that, in contrast to fibroblasts, breast cancer cells can endocytose the secreted pro-cathepsin D by a cell surface receptor that is different from the mannose-6-phosphate receptors or other lectins. The nature of this alternative receptor and its significance in the action of secreted pro-cathepsin D remain to be elucidated.
J Cell Sci 1998 Sep
PMID:Endocytosis of pro-cathepsin D into breast cancer cells is mostly independent of mannose-6-phosphate receptors. 970 53


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